FI63587C - Foerfarande foer framstaellning av anti-inflammatoriska halogenerade 4-hydroxi-2-alkyl-3-karbamoyl-2h-tieno-1,2-tiazin-1,1-dioxidderivat - Google Patents
Foerfarande foer framstaellning av anti-inflammatoriska halogenerade 4-hydroxi-2-alkyl-3-karbamoyl-2h-tieno-1,2-tiazin-1,1-dioxidderivat Download PDFInfo
- Publication number
- FI63587C FI63587C FI782737A FI782737A FI63587C FI 63587 C FI63587 C FI 63587C FI 782737 A FI782737 A FI 782737A FI 782737 A FI782737 A FI 782737A FI 63587 C FI63587 C FI 63587C
- Authority
- FI
- Finland
- Prior art keywords
- methyl
- pyridyl
- formula
- thiazine
- hydroxy
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 16
- 230000003110 anti-inflammatory effect Effects 0.000 title claims description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 60
- -1 2-thiazolyl Chemical group 0.000 claims description 56
- 150000001875 compounds Chemical class 0.000 claims description 28
- 239000000203 mixture Substances 0.000 claims description 20
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 10
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical group N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 claims description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 claims description 3
- GXBZUQWRRATBGE-UHFFFAOYSA-N 6-chloro-4-hydroxy-2-methyl-1,1-dioxo-n-pyridin-2-ylthieno[3,2-e]thiazine-3-carboxamide Chemical compound OC=1C=2C=C(Cl)SC=2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 GXBZUQWRRATBGE-UHFFFAOYSA-N 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Chemical group 0.000 claims description 3
- 238000002425 crystallisation Methods 0.000 claims description 3
- 230000008025 crystallization Effects 0.000 claims description 3
- 150000002081 enamines Chemical class 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 3
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 3
- RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 claims description 2
- MOJZGQZFNUKJHE-UHFFFAOYSA-N ClC=1SC=C2C(=C(N(S(C21)(=O)=O)C)C(=O)NC2=CC=CC=C2)O Chemical compound ClC=1SC=C2C(=C(N(S(C21)(=O)=O)C)C(=O)NC2=CC=CC=C2)O MOJZGQZFNUKJHE-UHFFFAOYSA-N 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims 2
- 238000009472 formulation Methods 0.000 claims 2
- 108010002352 Interleukin-1 Proteins 0.000 claims 1
- 239000002738 chelating agent Substances 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 239000003086 colorant Substances 0.000 claims 1
- 230000003301 hydrolyzing effect Effects 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000000376 reactant Substances 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 91
- 239000000243 solution Substances 0.000 description 70
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 49
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 40
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 33
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
- 238000003756 stirring Methods 0.000 description 29
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- 239000012074 organic phase Substances 0.000 description 16
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- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 238000002844 melting Methods 0.000 description 15
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- 239000002904 solvent Substances 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
- 239000002244 precipitate Substances 0.000 description 11
- 229910052938 sodium sulfate Inorganic materials 0.000 description 11
- 235000011152 sodium sulphate Nutrition 0.000 description 11
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- 239000008346 aqueous phase Substances 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- 239000005995 Aluminium silicate Substances 0.000 description 7
- 235000012211 aluminium silicate Nutrition 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 6
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- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
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- 239000002585 base Substances 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
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- 239000000741 silica gel Substances 0.000 description 5
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- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- 208000000114 Pain Threshold Diseases 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
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- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
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- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 230000008961 swelling Effects 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
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- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
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- 238000001035 drying Methods 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
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- WLHQHAUOOXYABV-UHFFFAOYSA-N lornoxicam Chemical compound OC=1C=2SC(Cl)=CC=2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 WLHQHAUOOXYABV-UHFFFAOYSA-N 0.000 description 3
- DDUIDBHEVOSXIL-UHFFFAOYSA-N methyl 4-acetamido-5-chlorothiophene-3-carboxylate Chemical compound COC(=O)C1=CSC(Cl)=C1NC(C)=O DDUIDBHEVOSXIL-UHFFFAOYSA-N 0.000 description 3
- 229960002895 phenylbutazone Drugs 0.000 description 3
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000001632 sodium acetate Substances 0.000 description 3
- 235000017281 sodium acetate Nutrition 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- YXMHAMMSBBVRKK-UHFFFAOYSA-N 2,5-dibromo-n-methylthiophene-3-sulfonamide Chemical compound CNS(=O)(=O)C=1C=C(Br)SC=1Br YXMHAMMSBBVRKK-UHFFFAOYSA-N 0.000 description 2
- NXEZMVJAZXKXHR-UHFFFAOYSA-N 2,5-dibromothiophene-3-sulfonyl chloride Chemical compound ClS(=O)(=O)C=1C=C(Br)SC=1Br NXEZMVJAZXKXHR-UHFFFAOYSA-N 0.000 description 2
- DXJQHGVGUCGFFW-UHFFFAOYSA-N 2,5-dichloro-n-methylthiophene-3-sulfonamide Chemical compound CNS(=O)(=O)C=1C=C(Cl)SC=1Cl DXJQHGVGUCGFFW-UHFFFAOYSA-N 0.000 description 2
- JJKSHSHZJOWSEC-UHFFFAOYSA-N 2,5-dichlorothiophene-3-sulfonyl chloride Chemical compound ClC1=CC(S(Cl)(=O)=O)=C(Cl)S1 JJKSHSHZJOWSEC-UHFFFAOYSA-N 0.000 description 2
- MESFXNGUDNODTJ-UHFFFAOYSA-N 2h-thiazine 1,1-dioxide Chemical compound O=S1(=O)NC=CC=C1 MESFXNGUDNODTJ-UHFFFAOYSA-N 0.000 description 2
- ZODFXZKQMZHZIC-UHFFFAOYSA-N 5-chloro-2-chlorosulfonylthiophene-3-carbonyl chloride Chemical compound ClC(=O)C=1C=C(Cl)SC=1S(Cl)(=O)=O ZODFXZKQMZHZIC-UHFFFAOYSA-N 0.000 description 2
- GMZNETLJONKHHD-UHFFFAOYSA-N 5-chloro-2-sulfothiophene-3-carboxylic acid Chemical compound OC(=O)C=1C=C(Cl)SC=1S(O)(=O)=O GMZNETLJONKHHD-UHFFFAOYSA-N 0.000 description 2
- SRXBPROHRKDGBA-UHFFFAOYSA-N 5-chloro-3-(methylsulfamoyl)thiophene-2-carboxylic acid Chemical compound CNS(=O)(=O)C=1C=C(Cl)SC=1C(O)=O SRXBPROHRKDGBA-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
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- 150000001298 alcohols Chemical class 0.000 description 2
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- 230000000202 analgesic effect Effects 0.000 description 2
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- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
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- 239000012043 crude product Substances 0.000 description 2
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- 238000002474 experimental method Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- COQRGFWWJBEXRC-UHFFFAOYSA-N hydron;methyl 2-aminoacetate;chloride Chemical compound Cl.COC(=O)CN COQRGFWWJBEXRC-UHFFFAOYSA-N 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
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- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- YTCYCGMTLFBYJK-UHFFFAOYSA-N methyl 4-amino-5-chlorothiophene-3-carboxylate;hydrochloride Chemical compound Cl.COC(=O)C1=CSC(Cl)=C1N YTCYCGMTLFBYJK-UHFFFAOYSA-N 0.000 description 2
- KSYKCHQAUUQCAZ-UHFFFAOYSA-N methyl 5-chloro-2-chlorosulfonylthiophene-3-carboxylate Chemical compound COC(=O)C=1C=C(Cl)SC=1S(Cl)(=O)=O KSYKCHQAUUQCAZ-UHFFFAOYSA-N 0.000 description 2
- QPZOBNQJSPOUQK-UHFFFAOYSA-N methyl 5-chloro-4-[(2-methoxy-2-oxoethyl)sulfamoyl]thiophene-3-carboxylate Chemical compound COC(=O)CNS(=O)(=O)C1=C(Cl)SC=C1C(=O)OC QPZOBNQJSPOUQK-UHFFFAOYSA-N 0.000 description 2
- SESOBZIEOHIQAB-UHFFFAOYSA-N methyl 6-bromo-4-hydroxy-2-methyl-1,1-dioxothieno[2,3-e]thiazine-3-carboxylate Chemical compound O=S1(=O)N(C)C(C(=O)OC)=C(O)C2=C1C=C(Br)S2 SESOBZIEOHIQAB-UHFFFAOYSA-N 0.000 description 2
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- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 1
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 1
- TVMLIARKUYLRRZ-UHFFFAOYSA-N 2,5-dibromothiophene-3-sulfonic acid Chemical compound OS(=O)(=O)C=1C=C(Br)SC=1Br TVMLIARKUYLRRZ-UHFFFAOYSA-N 0.000 description 1
- FGYBDASKYMSNCX-UHFFFAOYSA-N 2,5-dichlorothiophene Chemical compound ClC1=CC=C(Cl)S1 FGYBDASKYMSNCX-UHFFFAOYSA-N 0.000 description 1
- FBUUZRITKBLZJX-UHFFFAOYSA-N 2,5-dichlorothiophene-3-carboxylic acid Chemical compound OC(=O)C=1C=C(Cl)SC=1Cl FBUUZRITKBLZJX-UHFFFAOYSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- TZIJDLHRFZUDHD-UHFFFAOYSA-N 2h-thieno[2,3-e]thiazine Chemical class C1=CNSC2=C1SC=C2 TZIJDLHRFZUDHD-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- KYZYXLMNKITJME-UHFFFAOYSA-N 6-bromo-4-hydroxy-2-methyl-1,1-dioxo-n-pyridin-2-ylthieno[2,3-e]thiazine-3-carboxamide Chemical compound OC=1C=2SC(Br)=CC=2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 KYZYXLMNKITJME-UHFFFAOYSA-N 0.000 description 1
- WXBSBWNSQURCKO-UHFFFAOYSA-N 6-chloro-2-methyl-1,1-dioxo-3h-thieno[3,2-e]thiazin-4-one Chemical compound O=S1(=O)N(C)CC(=O)C2=C1SC(Cl)=C2 WXBSBWNSQURCKO-UHFFFAOYSA-N 0.000 description 1
- QSROMHGADXCEBY-UHFFFAOYSA-N 6-chloro-4-hydroxy-2-methyl-n-pyridin-2-ylthieno[2,3-e]thiazine-3-carboxamide Chemical compound CN1SC=2C=C(Cl)SC=2C(O)=C1C(=O)NC1=CC=CC=N1 QSROMHGADXCEBY-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 241000220479 Acacia Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- GIVOBELGYFBNEU-UHFFFAOYSA-N COC(=O)C=1SC(=C(C1C)S(N)(=O)=O)Cl Chemical compound COC(=O)C=1SC(=C(C1C)S(N)(=O)=O)Cl GIVOBELGYFBNEU-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
- JJHSSBDCKBGFJG-UHFFFAOYSA-N Cl.Cl.CNCC(=O)NC1=CC=CC=C1 Chemical compound Cl.Cl.CNCC(=O)NC1=CC=CC=C1 JJHSSBDCKBGFJG-UHFFFAOYSA-N 0.000 description 1
- NODCUKPOZMVESG-UHFFFAOYSA-N ClC1=CC(C(S1)(S(=O)(=O)O)Cl)C(=O)O Chemical compound ClC1=CC(C(S1)(S(=O)(=O)O)Cl)C(=O)O NODCUKPOZMVESG-UHFFFAOYSA-N 0.000 description 1
- ONXJFJWVGDCGAM-UHFFFAOYSA-N ClC1=CC2=C(CC(N(S2)C)(C(=O)OC)O)S1 Chemical compound ClC1=CC2=C(CC(N(S2)C)(C(=O)OC)O)S1 ONXJFJWVGDCGAM-UHFFFAOYSA-N 0.000 description 1
- GRUMAMVLDOJXMR-UHFFFAOYSA-N ClC=1SC=C2CC(N(S(C21)(=O)=O)C)(C(NC2=NC=CC=C2)=O)O Chemical compound ClC=1SC=C2CC(N(S(C21)(=O)=O)C)(C(NC2=NC=CC=C2)=O)O GRUMAMVLDOJXMR-UHFFFAOYSA-N 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 1
- 239000005751 Copper oxide Substances 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- 229910021592 Copper(II) chloride Inorganic materials 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- UZIWVVYLSOYBJI-UHFFFAOYSA-N S(=O)(=O)(O)Cl.C(=O)(OC)C1=CSC(=C1)Cl Chemical compound S(=O)(=O)(O)Cl.C(=O)(OC)C1=CSC(=C1)Cl UZIWVVYLSOYBJI-UHFFFAOYSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 230000002429 anti-coagulating effect Effects 0.000 description 1
- 230000003501 anti-edematous effect Effects 0.000 description 1
- 230000003356 anti-rheumatic effect Effects 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 229910000431 copper oxide Inorganic materials 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
- YDGMIJCIBXSCQR-UHFFFAOYSA-N methyl 2-iodoacetate Chemical compound COC(=O)CI YDGMIJCIBXSCQR-UHFFFAOYSA-N 0.000 description 1
- TXBKPJRPOSEUHU-UHFFFAOYSA-N methyl 4-[(2-anilino-2-oxoethyl)-methylsulfamoyl]-5-chlorothiophene-3-carboxylate Chemical compound C(=O)(OC)C1=CSC(=C1S(=O)(=O)N(CC(=O)NC1=CC=CC=C1)C)Cl TXBKPJRPOSEUHU-UHFFFAOYSA-N 0.000 description 1
- SCVSZCZILRQRGM-UHFFFAOYSA-N methyl 4-[[(2-anilino-2-oxoethyl)amino]methylsulfonyl]-5-chlorothiophene-3-carboxylate Chemical compound COC(=O)C1=CSC(=C1S(=O)(=O)CNCC(=O)NC1=CC=CC=C1)Cl SCVSZCZILRQRGM-UHFFFAOYSA-N 0.000 description 1
- AVVROEVEDPDFTH-UHFFFAOYSA-N methyl 4-acetamidothiophene-3-carboxylate Chemical compound COC(=O)C1=CSC=C1NC(C)=O AVVROEVEDPDFTH-UHFFFAOYSA-N 0.000 description 1
- XPJZPHCNBFFGDB-UHFFFAOYSA-N methyl 5-chloro-3-(methylsulfamoyl)thiophene-2-carboxylate Chemical compound CNS(=O)(=O)C=1C=C(Cl)SC=1C(=O)OC XPJZPHCNBFFGDB-UHFFFAOYSA-N 0.000 description 1
- XYKHBPLPVNNASM-UHFFFAOYSA-N methyl 6-chloro-4-hydroxy-1,1-dioxo-2h-thieno[3,2-e]thiazine-3-carboxylate Chemical compound O=S1(=O)NC(C(=O)OC)=C(O)C2=C1SC(Cl)=C2 XYKHBPLPVNNASM-UHFFFAOYSA-N 0.000 description 1
- HITUAYIBHWKKFU-UHFFFAOYSA-N methyl 6-chloro-4-hydroxy-2-methyl-1,1-dioxothieno[2,3-e]thiazine-3-carboxylate Chemical compound O=S1(=O)N(C)C(C(=O)OC)=C(O)C2=C1C=C(Cl)S2 HITUAYIBHWKKFU-UHFFFAOYSA-N 0.000 description 1
- SMMQPPXVECBSSA-UHFFFAOYSA-N methyl 7-chloro-4-hydroxy-1,1-dioxo-2h-thieno[3,4-e]thiazine-3-carboxylate Chemical compound O=S1(=O)NC(C(=O)OC)=C(O)C2=CSC(Cl)=C21 SMMQPPXVECBSSA-UHFFFAOYSA-N 0.000 description 1
- OCHIQDGHEWIKTH-UHFFFAOYSA-N methyl 7-chloro-4-hydroxy-2-methyl-1,1-dioxothieno[3,4-e]thiazine-3-carboxylate Chemical compound O=S1(=O)N(C)C(C(=O)OC)=C(O)C2=CSC(Cl)=C21 OCHIQDGHEWIKTH-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 231100000862 numbness Toxicity 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 239000004289 sodium hydrogen sulphite Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/30—Hetero atoms other than halogen
- C07D333/34—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| LU78083 | 1977-09-06 | ||
| LU78083 | 1977-09-06 | ||
| CH790878 | 1978-07-21 | ||
| CH790878 | 1978-07-21 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI782737A7 FI782737A7 (fi) | 1979-03-07 |
| FI63587B FI63587B (fi) | 1983-03-31 |
| FI63587C true FI63587C (fi) | 1983-07-11 |
Family
ID=25702440
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI782737A FI63587C (fi) | 1977-09-06 | 1978-09-06 | Foerfarande foer framstaellning av anti-inflammatoriska halogenerade 4-hydroxi-2-alkyl-3-karbamoyl-2h-tieno-1,2-tiazin-1,1-dioxidderivat |
Country Status (28)
Families Citing this family (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2838377A1 (de) * | 1978-09-02 | 1980-03-20 | Thomae Gmbh Dr K | Neue 4-hydroxy-2h eckige klammer auf 1 eckige klammer zu benzothieno eckige klammer auf 2,3-e eckige klammer zu -1,2- thiazin-3-carboxamid-1,1-dioxide sowie deren salze, deren verwendung und verfahren zu ihrer herstellung |
| AU5811280A (en) * | 1979-06-13 | 1980-12-18 | F. Hoffmann-La Roche Ag | Thiazine derivatives |
| JPS58109492A (ja) * | 1981-12-22 | 1983-06-29 | Mitsui Toatsu Chem Inc | チエノチアジン誘導体およびそれを含有する医薬組成物 |
| DE3371082D1 (de) * | 1982-09-09 | 1987-05-27 | Hoffmann La Roche | Thieno(2,3-e)-1,2-thiazine derivatives |
| GR80576B (en) * | 1983-10-17 | 1984-11-29 | Fujisawa Pharmaceutical Co | Thiazine derivatives, process for preparation thereof and pharmaceutical composition comprising the same |
| US4551452A (en) * | 1983-12-21 | 1985-11-05 | Pfizer Inc. | Anti-inflammatory 2-methyl-2H-1,2-benzo-(or -thieno-)thiazine-3-carboxamide 1,1-dioxide derivatives, compositions, and method of use therefor |
| DE3346526C2 (de) * | 1983-12-22 | 1986-12-11 | A. Nattermann & Cie GmbH, 5000 Köln | Pharmazeutisches Präparat zur therapeutischen Behandlung von rheumatischen Erkrankungen |
| JPS60184077A (ja) * | 1984-02-23 | 1985-09-19 | フアイザー・インコーポレーテツド | 抗炎症性オキシム前駆薬 |
| US4656265A (en) * | 1984-06-21 | 1987-04-07 | Pfizer Inc. | Cyclic prodrugs of antiinflammatory oxicams |
| US4623486A (en) | 1985-05-29 | 1986-11-18 | Pfizer Inc. | [4-substituted benzoyloxy]-N-substituted-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxides having anti-arthritic activity |
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| CN108218895B (zh) * | 2018-04-13 | 2019-06-18 | 北京金城泰尔制药有限公司沧州分公司 | 一锅法合成氯诺昔康中间体的方法 |
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| GB1308533A (en) | 1969-06-02 | 1973-02-21 | Pfizer | Benzothiazine dioxides as anti-thombotic agents |
| US3787324A (en) | 1971-03-01 | 1974-01-22 | Warner Lambert Co | 4-hydroxy-3-(3-isoxazolocarbamyl)-2h-1,2-benzothiazine 1,dioxides and process for their production |
| US3821211A (en) * | 1972-03-10 | 1974-06-28 | Warner Lambert Co | Process for the preparation of 4-hydroxy-3-(5-methyl-3-isoxazolycarbamoyl)-2-methyl-2h-1,2-benzothiazine 1,1-dioxide |
| CA1010990A (en) | 1973-06-06 | 1977-05-24 | Leopold H. O'donnell | Video tape recording animation system |
| IL47877A (en) * | 1974-08-26 | 1978-10-31 | Sparamedica Ag | Thienothiazine carboxamide derivatives,their manufacture and pharmaceutical compositions containing them |
| CA1066711A (en) * | 1974-08-26 | 1979-11-20 | Hoffmann-La Roche Limited | Thiophene derivatives |
| MC1135A1 (fr) * | 1976-02-23 | 1977-11-18 | Hoffmann La Roche | Derives de thiazine |
-
1978
- 1978-08-30 AU AU39389/78A patent/AU518216B2/en not_active Expired
- 1978-08-31 MC MC781322A patent/MC1212A1/xx unknown
- 1978-08-31 US US05/938,274 patent/US4180662A/en not_active Expired - Lifetime
- 1978-08-31 IL IL55465A patent/IL55465A/xx active IP Right Grant
- 1978-09-01 NZ NZ188320A patent/NZ188320A/xx unknown
- 1978-09-01 NL NL7809015A patent/NL7809015A/xx not_active Application Discontinuation
- 1978-09-04 HU HU78HO2099A patent/HU176979B/hu unknown
- 1978-09-04 GR GR57146A patent/GR73066B/el unknown
- 1978-09-04 PH PH21565A patent/PH13949A/en unknown
- 1978-09-05 NO NO783032A patent/NO149174C/no unknown
- 1978-09-05 SE SE7809348A patent/SE7809348L/xx unknown
- 1978-09-05 GB GB7835571A patent/GB2003877B/en not_active Expired
- 1978-09-05 ES ES473074A patent/ES473074A1/es not_active Expired
- 1978-09-05 JP JP10820378A patent/JPS5448792A/ja active Granted
- 1978-09-05 IE IE1788/78A patent/IE47261B1/en not_active IP Right Cessation
- 1978-09-05 CS CS785744A patent/CS202019B2/cs unknown
- 1978-09-05 AT AT0642178A patent/AT364851B/de not_active IP Right Cessation
- 1978-09-05 PT PT68515A patent/PT68515A/pt unknown
- 1978-09-05 CA CA310,603A patent/CA1103246A/en not_active Expired
- 1978-09-05 DK DK392778A patent/DK148280C/da active
- 1978-09-06 BR BR7805845A patent/BR7805845A/pt unknown
- 1978-09-06 FI FI782737A patent/FI63587C/fi not_active IP Right Cessation
- 1978-09-06 DE DE19782838851 patent/DE2838851A1/de not_active Withdrawn
- 1978-09-06 AR AR273600A patent/AR222472A1/es active
- 1978-09-06 IT IT27396/78A patent/IT1099046B/it active Protection Beyond IP Right Term
- 1978-09-06 DE DE7878100832T patent/DE2861316D1/de not_active Expired
- 1978-09-06 EP EP78100832A patent/EP0001113B1/de not_active Expired
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1985
- 1985-01-03 HK HK10/85A patent/HK1085A/xx not_active IP Right Cessation
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1998
- 1998-01-30 LU LU90207C patent/LU90207I2/fr unknown
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